Background: There are increasing data suggesting the involvement of the immune system in narcolepsy. The co-occurrence of narcolepsy with other autoimmune disorders (including multiple sclerosis, MS) is rare.

Methods: International multicenter sleep center survey and literature review on narcolepsy with (NC) and without (NwC) cataplexy.

Results: A total of 26 patients (pts), 6 in the survey and 20 in the literature were found. Two different types of association were identified: (1) Symptomatic type (5 pts): MS preceding the onset of narcolepsy, which was always without cataplexy (NwC); sleep onset REM episodes (SOREM) and hypocretin deficiency were observed in some, and lesions in the hypothalamus in all patients. (2) Coexisting type (18 pts): MS preceding or following the appearance of NC with SOREM, hypocretin deficiency but no lesions in the hypothalamus. A positive effect of steroids, immunoglobulins or natalizumab on narcolepsy symptoms was observed in four patients.

Conclusions: Narcolepsy and MS are rarely associated. In addition to NwC secondary to hypothalamic demyelination, some patients present a coexistence of MS with NC without detectable hypothalamic lesions. The rarity of reports on this association probably reflects underrecognition. The elucidation of underlying genetic and immune mechanisms needs further studies.